AB0039 MONOCYTE EXTRACELLULAR TRAPS: A NEW POTENTIAL DIAGNOSTIC BIOMARKER IN RHEUMATOID ARTHRITIS?
Authors: I. Zborovskaya, S. Bedina, E. Mozgovaya, A. Trofimenko, M. Mamus, S. Spitsina
Journal: Annals of the Rheumatic Diseases (2022)

Background Studies demonstrating the important role of neutrophil extracellular traps (NETs) in the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA), have been published extensively in recent years. The researchers are also discussing the possibility of considering NET as a source of potential diagnostic biomarker in RA. As compared with NETs, the monocyte extracellular traps (METs) formation by mononuclear phagocytes, although they have also been implicated in the development of autoimmune reactions, has been studied insufficiently. No studies have been reported on the MET formation in active RA patients. Objectives Assesssment of METs generation by peripheral blood monocytes from RA patients in association with the disease exacerbation. Methods The research was carried out in agreement with the WMA Declaration of Helsinki principles after the local ethical board approval. Circulating monocytes were isolated with one-step density gradient centrifugation using double layers of the in-lab-made ficoll-amidotrizoate gradient. Composition of isolated cellular fractions, their viability, and non-specific activation were evaluated by light microscopy using common Romanowsky-Giemsa staining, trypan blue exclusion test as well as NBT test. METs were induced by LPS. Monocyte fractions contained low extents of activated and dead cells. Spontaneous and induced formation of extracellular traps was assessed using fluorescence microscopy [1]. Results were presented as values (95%CI). Results 30 healthy volunteers (9 males and 21 females, mean age 37.2 years) were enrolled as a reference group. 37 patients (6 males and 31 females, mean age 42.7 years) with verified RA according to the ACR/EULAR 2010 criteria were included in the study. RA disease activity was assessed using DAS28 score did not exceeded 2.6 in every patient at the inclusion timepoint. In 16 (15.4%) patients, the activity of DAS 28 exceeded 3.2 at subsequent visits (after 3, 8 and 12 months). Spontaneous and induced MET formation by isolated monocytes in RA patients (DAS 28&lt;2.6) was 8.7 (8.3-9.1)% and 26.2 (24.5-27.9)%, respectively. Spontaneous and induced MET formation by isolated monocytes in RA patients (DAS 28&gt;3.2) was 18.1 (17.8-18.4)% and 38.2 (38.0-38.4)%, respectively. Spontaneous and induced MET formation by isolated neutrophils in active RA patients (DAS 28&gt;3.2) was significantly higher than in inactive RA patients and in comparison to the reference group. Induced MET formation was also significantly higher than spontaneous one (р&lt;0.05). Monocytes did not demonstrate any difference between ACPA-positive and ACPA-negative RA patients in their MET production. The growth rate of spontaneous MET formation was 114.7%, for induced MET formation – 44.2%. The growth rate of spontaneous MET formation is 2.6 times higher than the induced MET formation. Conclusion METs formation by isolated monocytes can be considered as a new potential diagnostic biomarker associated with RA flare. Further study of the mechanisms of MET formation and their composition may improve our understanding of the role of monocytes and METs in the pathogenesis of RA. References [1]Bedina S., et al. Medical immunology 2021; 23(5):1165-1170. Disclosure of Interests None declared